fluticasone and Lung-Diseases

In a double blind randomised controlled trial, 30 infants with chronic lung disease received fluticasone propionate or placebo for one year. There were no significant differences between treatment groups in the incidence of any day or night time symptoms or any other outcome measures.

Topics: Administration, Inhalation; Administration, Topical; Androstadienes; Anti-Inflammatory Agents; Bronchodilator Agents; Double-Blind Method; Female; Fluticasone; Gestational Age; Glucocorticoids; Humans; Infant; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Lung Diseases; Male; Oxygen; Respiration Disorders

To evaluate the efficacy of inhaled fluticasone propionate (Flovent) as prophylaxis against delayed pulmonary toxicity syndrome (DPTS) and decline in pulmonary function in breast cancer patients undergoing high-dose chemotherapy with the conditioning regimen of cyclophosphamide, cisplatin, and carmustine (CPB) followed by autologous stem cell transplantation (ASCT).. Sixty-three consecutive patients with multinode-positive or metastatic breast cancer undergoing high-dose chemotherapy with CPB and ASCT who were treated at the Duke University Adult Bone Marrow Transplant Program. All patients were started on inhaled fluticasone propionate, 880 microg every 12 hours, for 12 weeks from the start date of their CPB conditioning regimen. Pulmonary function tests (PFTs) with a single-breath diffusing capacity of carbon monoxide (DLCO) were performed pre-ASCT as well as approximately 6 and 12 weeks post-ASCT. DPTS was defined as follows: (1) development of a nonproductive cough and dyspnea with or without fever, plus a fall in DLCO to less than 60% predicted; or (2) decline in DLCO to less than 50% predicted with or without symptoms.. Pulmonary function tests were done on all patients pre-ASCT, on 56 of the 63 patients at a median of 44 days (range, 25 to 73 days) post-ASCT, and on 51 of the 63 patients at a median of 96 days (range, 50 to 190 days) post-ASCT. The PFTs showed an average of an 8% (+/-26%) and 21% (+/-22%) decline in DLCO. These declines compare favorably with our historical control group of 45 consecutive breast cancer patients undergoing ASCT with CPB as a conditioning regimen, who experienced average declines in DLCO of 29% (+/-18%) (P < .001) and 33% (+/-18%) (P < .001) at comparable time periods post-ASCT. Delayed pulmonary toxicity syndrome occurred in 35% of treated patients compared to 73% of the historical controls (P = .0003). No patients died of DPTS or pulmonary problems, and there were no fungal pneumonias.. Inhaled fluticasone propionate may decrease the incidence of DPTS in patients treated with CPB as a conditioning regimen for ASCT, as well as help to preserve pulmonary function as measured by DLCO. These results are worthy of further study in a randomized clinical trial.

Topics: Administration, Inhalation; Adult; Aged; Androstadienes; Anti-Inflammatory Agents; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Cohort Studies; Female; Fluticasone; Hematopoietic Stem Cell Transplantation; Humans; Incidence; Lung Diseases; Middle Aged; Respiratory Function Tests; Steroids; Syndrome; Transplantation, Autologous; Treatment Outcome

Most attempts to achieve sustained drug delivery to pulmonary tissues using nanoparticles have focused on mucoadhesive particles (MAP). However, MAP become trapped in the luminal mucus layer and, as a result, are largely eliminated from the respiratory tract by mucociliary escalator and expiratory clearance, which undermines their sustained release potential. Recent studies have shown that mucus-penetrating particles (MPP) engineered to diffuse through mucus can avoid rapid mucociliary clearance in vivo and persist in the lung longer. Nonetheless, it has not been confirmed that MPP encapsulating small molecules can sustain drug release in the lung longer than MAP of similar size and core composition. As a proof of concept, we encapsulated fluticasone propionate (FP) into poly(lactide)-based MPP and MAP (both ∼ 200 nm diameter, ∼ 30-35% drug loading) and evaluated their pulmonary residence by measuring FP levels in mouse lungs over 24h following intratracheal instillation. Furthermore, we evaluated the duration of action of FP MPP in a rat lung inflammation model compared to that of a non-encapsulated FP control. In rodents, pulmonary delivery of FP formulated as MPP provided a 60% higher local exposure compared to MAP and extended the single dose efficacy by at least 16 h compared to non-encapsulated FP.

Topics: Administration, Inhalation; Animals; Anti-Inflammatory Agents; Delayed-Action Preparations; Drug Delivery Systems; Female; Fluticasone; Humans; Inflammation; Lipopolysaccharides; Lung; Lung Diseases; Male; Mice; Mucus; Nanoparticles; Polyesters; Rats, Inbred Lew

Currently, functional assessment to monitor therapeutic response in feline lower airway disease (FLAD) has limited application.. To evaluate if expiratory indices derived from pseudo-tidal breathing flow-volume loop (pTBFVL) representing lower airway obstruction would decrease after clinical improvement and to investigate the correlation between functional phenotype and inflammatory cell type in bronchoalveolar lavage (BAL) fluid.. Nineteen client-owned cats with FLAD.. Prospective observational study. Functional assessment with pTBFVL indices (eg, peak to mid-expiratory flow; PEF/EF50) and conventional barometric whole body plethysmography (BWBP) parameters (eg, enhanced pause) was carried out before receiving treatment. BAL was performed to analyze inflammatory cell types. Signs were assessed by scoring. The cats were treated with glucocorticoids daily and functional testing was repeated.. Loop indices PEF/EF50 and PEF/EF25 were significantly decreased after treatment (P < .001). Conventional BWBP parameters were not significantly different before and after treatment. Cats with PEF/EF50 > 1.51 before treatment had a significantly higher granulocyte (eosinophil plus neutrophil) percentage in BAL fluid (P = .014). Granulocyte percentage in BAL fluid was strongly correlated with PEF/EF25 (P = .001, rs = 0.74) and moderately correlated with PEF/EF50 (P = .022, rs = 0.57), whereas eosinophil or neutrophil percentage alone had no significant correlation with functional parameters.. Functional parameters including PEF/EF50 and PEF/EF25 can be used for monitoring therapeutic response. The presence of airflow limitation during mid- to late expiration is affected by the overall extent of granulocyte infiltration.

Topics: Androstadienes; Animals; Anti-Inflammatory Agents; Bronchoalveolar Lavage Fluid; Cat Diseases; Cats; Fluticasone; Inflammation; Lung Diseases; Prednisolone; Respiratory Therapy

The Inhaled Steroids in Obstructive Lung Disease (ISOLDE) study was a trial that randomised 752 patients with moderate to severe COPD to fluticasone propionate 1000 mcg/day or placebo for three years. We aimed to examine the causes of death of the ISOLDE participants after the original three up to 13 years post-randomisation. Death certificates were obtained either from the NHS Strategic Tracing Service or from the Office of National statistics. Deaths were classified according to the trial protocol. In the subsample of 375 participants from the seven ISOLDE original centers where complete extended follow-up was conducted, the factors associated with observed higher mortality (p<0.05) were male gender, older age and more severe COPD. Causes of death were; 107 (52%) respiratory, 38 (18%) cardiac, 29 (14%) lung cancer, 16 (8%) other cancer and 16 (8%) other causes. The percentage of respiratory-related deaths increased during the follow-up period; from 46% within the three-year trial, to 48% after 3-6 years, 57% after 6-9 years, and 60% after 9-13 years of follow-up (p for trend<0.05). We conclude that participants' survival is poor (only 44% in the 13 years after the ISOLDE trial), and that respiratory-related illnesses were the most frequent causes of death in patients with moderate to severe COPD.

Topics: Age Factors; Aged; Androstadienes; Female; Fluticasone; Follow-Up Studies; Humans; Kaplan-Meier Estimate; Lung Diseases; Male; Middle Aged; Prognosis; Pulmonary Disease, Chronic Obstructive; Randomized Controlled Trials as Topic; Risk; Sex Factors; Smoking

Work in humans and laboratory animals has identified a central role for cytokines and chemokines in development and persistence of lower airway inflammation. The objectives of this study were to determine interleukin (IL)-1 beta, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha induction in bronchoalveolar lavage (BAL) of control horses and horses with heaves both during remission and exacerbation of the disease, and to determine the effect of therapy with inhaled fluticasone propionate on the cytokine profile of horses with heaves. IL-1 beta and TNF-alpha mRNA expression was significantly higher in horses with heaves after exposure to moldy hay compared to either values obtained during clinical remission or to healthy controls. IL-8 mRNA expression and protein concentrations were significantly higher in horses with heaves than in controls. Both IL-4 and IFN-gamma mRNA expression was increased at various times in heaves-susceptible horses compared to controls. IL-2, IL-5 and IL-10 mRNA expression was not detected in BAL cells of either group. Therapy with inhaled fluticasone propionate after induction of a severe heaves exacerbation resulted in complete resolution of clinical signs, normalization of pulmonary function tests, and significant decrease in BAL neutrophilia. This was associated with a significant decrease in IL-4 mRNA expression and increase in IFN-gamma/IL-4 ratio in horses with heaves. These results demonstrate the clinical efficacy of inhaled fluticasone propionate for the treatment of heaves and suggest a role for cytokines in the development of lower airway inflammation in heaves-susceptible horses.

Topics: Androstadienes; Animals; Anti-Inflammatory Agents; Bronchoalveolar Lavage Fluid; Cell Count; Cytokines; Fluticasone; Horse Diseases; Horses; Lung Diseases; Respiratory Function Tests; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Statistics, Nonparametric

Topics: Administration, Inhalation; Androstadienes; Anti-Inflammatory Agents; Clinical Trials as Topic; Fluticasone; Humans; Lung Diseases